Important forms of human cancer stem from exposure to mutagens and carcinogens and in particular to the intake of such agents in foods. A new field of research was opened with the discovery in 1977 that frying or broiling, or similar high temperature modes of cooking, produce carcinogens from precursors in foods, particularly foods such as meat or fish. Sugimura T: Carcinogenicity of mutagenic heterocyclic amines formed during the cooking process. Mutat. Res. 150.33-41, 1985. Research on these powerful mutagens has demonstrated that these chemicals are carcinogens for target organs such as the breast and intestinal tract. Tanaka T., Barness W. S., Weisburger J. H., Williams G. M.: Multipotential carcinogenicity of the fried food mutagen 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) in rats. Jap. J. Cancer Res. (Gann) 76:P570-576, 1985.
In the field of cancer research, Applicants have been engaged in developing reliable information on causes of cancer as sound means of preventing cancer by avoiding or eliminating the causes so pinpointed. Weisburger J. H., Wynder E. L.: The role of genotoxic carcinogens and of promoters in carcinogenesis and in human cancer causation. Acta Pharmacologica et Toxicologica 55 (suppl II):53-68, 1984. Weisburger J. H.: Mechanisms of nutritional carcinogenesis associated with specific human cancers. ISI Atlas of Science: Pharmacology 1:162-167, 1987.
Based on many lines of evidence, including studies in epidemiology, geographic pathology, and laboratory studies, it has been demonstrated that certain nutritional parameters are involved in the causation of several of the important and major forms of human cancer, including cancer of the breast, pancreas, and intestinal tract. Weisburger J. H.: Mechanisms of nutritional carcinogenesis associated with specific human cancers. ISI Atlas of Science: Pharmacology 1:162-167, 1987. Reddy B. S., Cohen L. A., McCoy G. D., Hill P. Weisburger J. H., Wynder E. L.: Nutrition and its relationship to cancer. Adv. Cancer Res. 32:237-345, 1980. One area of research has demonstrated that the amount of total fat intake is associated with these kinds of cancer. It has been established that the role of fat is indirect through various mechanisms that act in enhancing or promoting such factors. Ready B. S., Cohen L. A., McCoy G. D., Hill P., Weisburger J. H., Wynder E. L.: Nutrition and its relationship to cancer. Adv. Cancer Res. 32:237-345, 1980. Such elements are not direct causes of cancer.
Until 1977, the actual specific cancer-causing entities for these target organs were not only known but also there was no working hypothesis as to their nature. This situation changed with the discovery by Takashi Sugimura, M.D. and his associates at the National Cancer Center Research Institute in Tokyo who discovered that the surface of fried fish and fried meat contained powerful mutagens, i.e., agents capable of changing the genetic apparatus of cells. Sugimura T., Nagao M., Kawachi T., Honda M., Yahagi T. Seino Y., Satos S., Matsukura N., Matsushima T., Shirai A., Sawamura M., Matsumoto H.: Mutagen-carcinogens in food, with special reference to highly mutagenic pyrolytic products in broiled foods. In Hiatt H. H., Watson J. D., K. D., Winsten J. A. (eds): Origins of Human Cancer, Book C, pp. 1561-1577. Cold Spring Harbor, N.Y.: Cold Spring Harbor Lab., 1977. A mutagenic agent is often found to be carcinogenic, i.e., cancer causing, and therefore any mutagen can be suspected of being potentially carcinogenic. In collaboration with Dr. Sugimura, Applicants established methods to separate and identify this novel class of mutagens, an activity that was successful. In the last ten years a number of mutagenic chemicals formed during the cooking (frying, broiling, baking) of protein-containing foods, especially fish and meat, were identified and were found to belong to a novel class of heterocyclic amines and imidazoazaarene compounds. Knudsen I. (Ed.): Genetic Toxicology of the Diet. New York: Alan Liss Inc., 1986. Hatch F. T. et al: Nishimura, S., Powrie, W. D. & Kolonel, L. N. (eds.) Dietary Mutagens, A Symposium I. Genetically relevant endpoints. Environmental Health Perspect. 67:3-157, 1986. Felton J. S., Knize M. G., Shen N. H., Lewis P. R., Andersen B. D., Happe J., Hatch F. T.: The isolation and identification of a new mutagen from fried ground beef: 2-amino-1-methyl-6-phenylimidazo-[4,5-b]pyridine (PhIP). Carcinogenesis 7:1081-1086, 1986. Vuolo L. L., Schuessler G. J.: Review: Putative mutagens and carcinogens in foods. VI. Protein pyrolysate products. Environ. Mutagenesis 7:577-598, 1985. A number of such compounds have found to be highly mutagenic. They were active in other tests delineating potential cancer-causing ability, and when tested in appropriate animal models were found to actually cause cancer in target organs such as breast, pancreas, and intestinal tract. Sugimura T.: Carcinogenicity of mutagenic heterocyclic amines formed during the cooking process. Mutat. Res. 150:33-41, 1985. Tanaka T., Barnes W. S., Weisburger J. H., Williams G. M.: Multipotential carcinogenicity of the fried food mutagen 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) in rats. Jap. 3. Cancer Res. (Gann) 76:570-576, 1985.
It was therefore postulated that cooking by broiling and frying of meats or fish leads to carcinogens that are cancer-causing agents for the organs of the intestinal tract and breast, with other dietary components such as the level and type of fat exerting an enhancing effect. Weisburger J. H.: Mechanisms of nutritional carcinogenesis associated with specific human cancers. ISI Atlas of Science: Pharmacology 1:162-167, 1987. In this general field, it has been accepted that prevention of important forms of cancer optimally consists of removing the carcinogens associated with each type of cancer from the environment. Therefore, Applicants have made great efforts to study the mode of formation of these mutagens and carcinogens during cooking. Applicants, as well as the group of Jagerstad in Sweden Taylor, Felton, Hatch and associates in California, and the group of Matsushima and Sugimura in Japan, have contributed to this field. Knudsen I. (Ed).): Genetic Toxology of the Diet. New York: Alan Liss Inc., 1986 (see above). Nishimura, S., Powrie, W. D. & Kolonel, L. N. (eds.) Food Mutagens, A Symposium I. Genetically relevant endopoints. Environmental Health Perspect. 67:3-157, 1986. Felton J. S., Knize M. G., Shen N. H., Lewis P. R., Andresen B. D., Happe J., Hatch F. T.: The isolation and identification of a new mutagen from fried ground beef: 2-amino-1-methyl-6-phenylimidazo-[4,5-b]pyridine (PhIP). Carcinogenesis 7:1081-1086, 1986. All those concerned with the mode of formation of these chemicals during cooking agree that an essential component is the presence of creatine or creatinine in the foodstuff. Vuolo L. L., Schuessler G. J.: Review: Putative mutagens and carcinogens in foods. VI. Protein pyrolysate products. Reutersward A. L., Skog K., Jagerstad: Effects of creatine and creatinine content on the mutagenic activity of meat extracts, bouillions and gravies from different sources. Fd. Chem. Toxic. 23:747-754, 1987. Creatinine reacts in a series of very complex interactions with certain precursors to form the mutagens and carcinogens typified by the family of aminomethylimidazoquinolines or quinoxalines and related aminoimidazoazaarenes. This entire field of research is only ten years old and relatively few institutions in the world have contributed to advances in this area. Knudsen I. (Ed.): Genetic Toxicology of the Diet. New York: Alan Liss Inc., 1986. Hatch F. T. et al.
Patents are known in which certain meats are treated for quite distinct, unrelated goals. These patents include U.S. Pat. No. 3,681,095 (Aug. 1972) involving the use of certain amino acids on meats to aid in preserving meats during dehydration and permitting ready reconstitution. Clearly, this patent does not deal with the specific use of indole-type amino acids in preventing the formation of mutagens as will be detailed below in the description of the invention.
U.S. Pat. No. 3,840,676 (Oct. 8, 1974) deals with the use of mixtures including certain amino acids to create a film at the surface of meats to prevent the putrefaction and oxidation of such meats. Clearly, this particular process does not have any relationship to the present invention dealing with the specific property of proline and tryptophan in blocking mutagen formation.
U.S. Pat. No. 3,911,146 (Oct. 7, 1975) uses certain vegetable ingredients and also amino acids to preserve the color of red meats as replacement for nitrite or nitrate. Clearly, this particular application of amino acids is distinct from the current finding that specific, indole ring-containing amino acids block the formation of mutagens.
U.S. Pat. No. 4,521,435 (June 4, 1985) deals with the application of a coating, including 30% by weight of dried powdered egg whites, to hamburger-type meat patties for the purpose of forming a coating to seal in the meat juices and thus reduce weight loss during cooking. Clearly, this particular process is quite distinct in purpose and application from the specific inhibition of mutagen and carcinogen formation during cooking by specific reactions between the compounds applied and components formed during cooking.